Allosteric modulation of retinal GABA receptors by ascorbic acid

Autores
Calero, Cecilia Ines; Vickers, Evan; Cid, Gustavo Moraga; Aguayo, Luis G.; von Gersdorff, Henrique; Calvo, Daniel Juan
Año de publicación
2011
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Ionotropic GABA receptors (GABAA and GABAC) belong to the Cys-loop receptor family of ligand-gated ion channels. GABAC receptors are highly expressed in the retina, mainly localized at the axon terminals of bipolar cells. Ascorbic acid, an endogenous redox agent, modulates the function of diverse proteins, and basal levels of ascorbic acid in the retina are very high. However, the effect of ascorbic acid on retinal GABA receptors has not been studied. Here we show that the function of GABAC and GABAA receptors is regulated by ascorbic acid. Patch-clamp recordings from bipolar cell terminals in goldfish retinal slices revealed that GABAC receptor-mediated currents activated by tonic background levels of extracellular GABA, and GABAC currents elicited by local GABA puffs, are both significantly enhanced by ascorbic acid. In addition, a significant rundown of GABA puff-evoked currents was observed in the absence of ascorbic acid. GABA-evoked Cl- currents mediated by homomeric ρ1 GABAC receptors expressed in Xenopus laevis oocytes were also potentiated by ascorbic acid in a concentration-dependent, stereo-specific, reversible, and voltage-independent manner. Studies involving the chemical modification of sulfhydryl groups showed that the two Cys-loop cysteines and histidine 141, all located in the ρ1 subunit extracellular domain, each play a key role in the modulation of GABAC receptors by ascorbic acid. Additionally, we show that retinal GABAA IPSCs and heterologously expressed GABAA receptor currents are similarly augmented by ascorbic acid. Our results suggest that ascorbic acid may act as an endogenous agent capable of potentiating GABAergic neurotransmission in the CNS.
Fil: Calero, Cecilia Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Vickers, Evan. Oregon Health and Science University; Estados Unidos
Fil: Cid, Gustavo Moraga. Universidad de Concepción; Chile
Fil: Aguayo, Luis G.. Universidad de Concepción; Chile
Fil: von Gersdorff, Henrique. Oregon Health and Science University; Estados Unidos
Fil: Calvo, Daniel Juan. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Materia
GABA RECEPTORS
REDOX MODULATION
ASCORBIC ACID
RETINA
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/79501
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/79501
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Allosteric modulation of retinal GABA receptors by ascorbic acidCalero, Cecilia InesVickers, EvanCid, Gustavo MoragaAguayo, Luis G.von Gersdorff, HenriqueCalvo, Daniel JuanGABA RECEPTORSREDOX MODULATIONASCORBIC ACIDRETINAhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Ionotropic GABA receptors (GABAA and GABAC) belong to the Cys-loop receptor family of ligand-gated ion channels. GABAC receptors are highly expressed in the retina, mainly localized at the axon terminals of bipolar cells. Ascorbic acid, an endogenous redox agent, modulates the function of diverse proteins, and basal levels of ascorbic acid in the retina are very high. However, the effect of ascorbic acid on retinal GABA receptors has not been studied. Here we show that the function of GABAC and GABAA receptors is regulated by ascorbic acid. Patch-clamp recordings from bipolar cell terminals in goldfish retinal slices revealed that GABAC receptor-mediated currents activated by tonic background levels of extracellular GABA, and GABAC currents elicited by local GABA puffs, are both significantly enhanced by ascorbic acid. In addition, a significant rundown of GABA puff-evoked currents was observed in the absence of ascorbic acid. GABA-evoked Cl- currents mediated by homomeric ρ1 GABAC receptors expressed in Xenopus laevis oocytes were also potentiated by ascorbic acid in a concentration-dependent, stereo-specific, reversible, and voltage-independent manner. Studies involving the chemical modification of sulfhydryl groups showed that the two Cys-loop cysteines and histidine 141, all located in the ρ1 subunit extracellular domain, each play a key role in the modulation of GABAC receptors by ascorbic acid. Additionally, we show that retinal GABAA IPSCs and heterologously expressed GABAA receptor currents are similarly augmented by ascorbic acid. Our results suggest that ascorbic acid may act as an endogenous agent capable of potentiating GABAergic neurotransmission in the CNS.Fil: Calero, Cecilia Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Vickers, Evan. Oregon Health and Science University; Estados UnidosFil: Cid, Gustavo Moraga. Universidad de Concepción; ChileFil: Aguayo, Luis G.. Universidad de Concepción; ChileFil: von Gersdorff, Henrique. Oregon Health and Science University; Estados UnidosFil: Calvo, Daniel Juan. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaSociety for Neuroscience2011-04info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/79501Calero, Cecilia Ines; Vickers, Evan; Cid, Gustavo Moraga; Aguayo, Luis G.; von Gersdorff, Henrique; et al.; Allosteric modulation of retinal GABA receptors by ascorbic acid; Society for Neuroscience; Journal of Neuroscience; 31; 26; 4-2011; 9672-96820270-6474CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3160198/info:eu-repo/semantics/altIdentifier/doi/10.1523/JNEUROSCI.5157-10.2011info:eu-repo/semantics/altIdentifier/url/https://www.jneurosci.org/content/31/26/9672info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-10T13:18:28Zoai:ri.conicet.gov.ar:11336/79501instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-10 13:18:28.412CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Allosteric modulation of retinal GABA receptors by ascorbic acid
title Allosteric modulation of retinal GABA receptors by ascorbic acid
spellingShingle Allosteric modulation of retinal GABA receptors by ascorbic acid
Calero, Cecilia Ines
GABA RECEPTORS
REDOX MODULATION
ASCORBIC ACID
RETINA
title_short Allosteric modulation of retinal GABA receptors by ascorbic acid
title_full Allosteric modulation of retinal GABA receptors by ascorbic acid
title_fullStr Allosteric modulation of retinal GABA receptors by ascorbic acid
title_full_unstemmed Allosteric modulation of retinal GABA receptors by ascorbic acid
title_sort Allosteric modulation of retinal GABA receptors by ascorbic acid
dc.creator.none.fl_str_mv Calero, Cecilia Ines
Vickers, Evan
Cid, Gustavo Moraga
Aguayo, Luis G.
von Gersdorff, Henrique
Calvo, Daniel Juan
author Calero, Cecilia Ines
author_facet Calero, Cecilia Ines
Vickers, Evan
Cid, Gustavo Moraga
Aguayo, Luis G.
von Gersdorff, Henrique
Calvo, Daniel Juan
author_role author
author2 Vickers, Evan
Cid, Gustavo Moraga
Aguayo, Luis G.
von Gersdorff, Henrique
Calvo, Daniel Juan
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv GABA RECEPTORS
REDOX MODULATION
ASCORBIC ACID
RETINA
topic GABA RECEPTORS
REDOX MODULATION
ASCORBIC ACID
RETINA
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Ionotropic GABA receptors (GABAA and GABAC) belong to the Cys-loop receptor family of ligand-gated ion channels. GABAC receptors are highly expressed in the retina, mainly localized at the axon terminals of bipolar cells. Ascorbic acid, an endogenous redox agent, modulates the function of diverse proteins, and basal levels of ascorbic acid in the retina are very high. However, the effect of ascorbic acid on retinal GABA receptors has not been studied. Here we show that the function of GABAC and GABAA receptors is regulated by ascorbic acid. Patch-clamp recordings from bipolar cell terminals in goldfish retinal slices revealed that GABAC receptor-mediated currents activated by tonic background levels of extracellular GABA, and GABAC currents elicited by local GABA puffs, are both significantly enhanced by ascorbic acid. In addition, a significant rundown of GABA puff-evoked currents was observed in the absence of ascorbic acid. GABA-evoked Cl- currents mediated by homomeric ρ1 GABAC receptors expressed in Xenopus laevis oocytes were also potentiated by ascorbic acid in a concentration-dependent, stereo-specific, reversible, and voltage-independent manner. Studies involving the chemical modification of sulfhydryl groups showed that the two Cys-loop cysteines and histidine 141, all located in the ρ1 subunit extracellular domain, each play a key role in the modulation of GABAC receptors by ascorbic acid. Additionally, we show that retinal GABAA IPSCs and heterologously expressed GABAA receptor currents are similarly augmented by ascorbic acid. Our results suggest that ascorbic acid may act as an endogenous agent capable of potentiating GABAergic neurotransmission in the CNS.
Fil: Calero, Cecilia Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Vickers, Evan. Oregon Health and Science University; Estados Unidos
Fil: Cid, Gustavo Moraga. Universidad de Concepción; Chile
Fil: Aguayo, Luis G.. Universidad de Concepción; Chile
Fil: von Gersdorff, Henrique. Oregon Health and Science University; Estados Unidos
Fil: Calvo, Daniel Juan. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
description Ionotropic GABA receptors (GABAA and GABAC) belong to the Cys-loop receptor family of ligand-gated ion channels. GABAC receptors are highly expressed in the retina, mainly localized at the axon terminals of bipolar cells. Ascorbic acid, an endogenous redox agent, modulates the function of diverse proteins, and basal levels of ascorbic acid in the retina are very high. However, the effect of ascorbic acid on retinal GABA receptors has not been studied. Here we show that the function of GABAC and GABAA receptors is regulated by ascorbic acid. Patch-clamp recordings from bipolar cell terminals in goldfish retinal slices revealed that GABAC receptor-mediated currents activated by tonic background levels of extracellular GABA, and GABAC currents elicited by local GABA puffs, are both significantly enhanced by ascorbic acid. In addition, a significant rundown of GABA puff-evoked currents was observed in the absence of ascorbic acid. GABA-evoked Cl- currents mediated by homomeric ρ1 GABAC receptors expressed in Xenopus laevis oocytes were also potentiated by ascorbic acid in a concentration-dependent, stereo-specific, reversible, and voltage-independent manner. Studies involving the chemical modification of sulfhydryl groups showed that the two Cys-loop cysteines and histidine 141, all located in the ρ1 subunit extracellular domain, each play a key role in the modulation of GABAC receptors by ascorbic acid. Additionally, we show that retinal GABAA IPSCs and heterologously expressed GABAA receptor currents are similarly augmented by ascorbic acid. Our results suggest that ascorbic acid may act as an endogenous agent capable of potentiating GABAergic neurotransmission in the CNS.
publishDate 2011
dc.date.none.fl_str_mv 2011-04
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/79501
Calero, Cecilia Ines; Vickers, Evan; Cid, Gustavo Moraga; Aguayo, Luis G.; von Gersdorff, Henrique; et al.; Allosteric modulation of retinal GABA receptors by ascorbic acid; Society for Neuroscience; Journal of Neuroscience; 31; 26; 4-2011; 9672-9682
0270-6474
CONICET Digital
CONICET
url http://hdl.handle.net/11336/79501
identifier_str_mv Calero, Cecilia Ines; Vickers, Evan; Cid, Gustavo Moraga; Aguayo, Luis G.; von Gersdorff, Henrique; et al.; Allosteric modulation of retinal GABA receptors by ascorbic acid; Society for Neuroscience; Journal of Neuroscience; 31; 26; 4-2011; 9672-9682
0270-6474
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3160198/
info:eu-repo/semantics/altIdentifier/doi/10.1523/JNEUROSCI.5157-10.2011
info:eu-repo/semantics/altIdentifier/url/https://www.jneurosci.org/content/31/26/9672
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Society for Neuroscience
publisher.none.fl_str_mv Society for Neuroscience
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 12.993085

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